tbuckley/cabot-search huggingface dataset:
Stent-in-stent deployment above the papilla to treat malignant hepatic hilar biliary obstruction using novel fully covered multi-hole metal stent
Authors: Hirotsugu Maruyama, Kojiro Tanoue, Tatsuya Kurokawa, Yoshinori Shimamoto, Yuki Ishikawa-Kakiya, Akira Higashimori, Yasuhiro Fujiwara
Journal: Endoscopy (2023)

Fully covered self-expandable metal stents (FCSEMSs) are usually used for malignant hilar biliary obstruction because they can be removed if required and provide longer stent patency by preventing tissue ingrowth [1] [2]; however, their use in the hepatic hilum carries the risk of blocking the side branches of the hepatic ducts and stent migration [3] [4] [5]. Furthermore, stent-in-stent techniques are unfeasible. A new FCSEMS with multiple holes was introduced to address these problems. We report successful stent-in-stent bilateral metal stent deployment using this novel FCSEMS (HANARO Biliary Multi-Hole NEO; M.I. Tech Co., Ltd, Pyeongtaek, South Korea) ([Fig. 1]) for malignant hilar biliary obstruction.
Contrast-enhanced endoscopic ultrasound and fine-needle biopsy of a rare mediastinal mass: a mediastinal schwannoma
Authors: Dario Ligresti, Dario Quintini, Ilaria Tarantino, Alessandro Bertani, Agita Jukna, Giacomo Emanuele Maria Rizzo, Mario Traina
Journal: Endoscopy (2023)

Contrast-enhanced endoscopic ultrasonography-guided fine-needle biopsy (CE-EUS-FNB) is an important, minimally invasive tool for the diagnosis of mediastinal masses. The specimen obtained allows a wider range of analyses to be performed and a better description of morphology and immunophenotype compared with fine-needle aspiration (FNA). The main advantages of CE-EUS include real-time imaging of microvascularity and microperfusion, and impressively good detail resolution [1].
A novel endoscopic ultrasound guided re-pancreaticogastrostomy using forward-viewing echoendoscope
Authors: Kosuke Maehara, Tetsuo Tamura, Kazuki Hirano, Daisuke Hattori, Yoshiki Sato, Rikako Koyama, Tsunao Imamura
Journal: Endoscopy (2023)

Recently, there has been a significant increase in the use of endoscopic ultrasound (EUS)-guided interventions, and several new EUS-guided drainage methods have been reported [1] [2] [3]. In the present case, we describe a novel technique for EUS-guided re-pancreaticogastrostomy using a forward-viewing echoendoscope.
Alignment Between 24-h Light-Dark and Activity-Rest Rhythms Is Associated With Diabetes and Glucose Metabolism in a Nationally Representative Sample of American Adults
Authors: Qian Xiao, John Durbin, Cici Bauer, Chris Ho Ching Yeung, Mariana G. Figueiro
Journal: Diabetes Care (2023)

OBJECTIVE The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations. RESEARCH DESIGN AND METHODS The analysis included ∼7,000 adults (aged 20–80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011–2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, respectively. We used multinomial logistic regression and multiple linear regression to study phasor magnitude and phasor angle in relation to diabetes (primary outcome) and multiple secondary biomarkers of glycemic control. RESULTS Lower alignment strength (i.e., a shorter phasor magnitude) and more delayed activity relative to the light cycle (i.e., a larger phasor angle) were both associated with diabetes. Specifically, compared with individuals in the quintiles indicating the most proper alignment (Q5 for phasor magnitude and Q1 for phasor angle), those in the quintiles with the most impaired alignment had a &amp;gt;70% increase in the odds of diabetes for phasor magnitude (odds ratio 1.76 [95% CI 1.39, 2.24]) and for phasor angle (1.73 [1.34, 2.25]). Similar associations were observed for biomarkers for glucose metabolism. The results were generally consistent across diverse sociodemographic and obesity groups. CONCLUSIONS The alignment pattern between 24-h activity-rest and light-dark cycles may be a critical factor in metabolic health.
Reply to Martinez-Garcia <i>et al.</i> and to Wang <i>et al.</i>
Authors: James P. Allinson, Ben H. Vlies, Simon E. Brill, Martin Law, Girvan Burnside, Lydia J. Finney, Luana Alves-Moreira, Peter M. A. Calverley, Paul P. Walker, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to Martinez-Garcia, et al. and Wang, et al.." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Long-Term Doxycycline Therapy for Stable Chronic Obstructive Pulmonary Disease: Do the Benefits Outweigh the Drawbacks?
Authors: Jingcun Wang, Qiming Gan, Haojie Zhang, Qiuyun Xing, Yanjuan Wu, Xiaofen Su, Nuofu Zhang, Kang Wu
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Long-Term Doxycycline Therapy for Stable COPD: Do the Benefits Outweigh the Drawbacks? ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation
Authors: Joshua M. Diamond, Edward Cantu, Carolyn S. Calfee, Michaela R. Anderson, Emily S. Clausen, Michael G. S. Shashaty, Andrew M. Courtwright, Laurel Kalman, Michelle Oyster, Maria M. Crespo, Christian A. Bermudez, Luke Benvenuto, Scott M. Palmer, Laurie D. Snyder, Matthew G. Hartwig, Jamie L. Todd, Keith Wille, Chadi Hage, John F. McDyer, Christian A. Merlo, Pali D. Shah, Jonathan B. Orens, Gundeep S. Dhillon, Ann B. Weinacker, Vibha N. Lama, Mrunal G. Patel, Jonathan P. Singer, Jesse Hsu, A. Russell Localio, Jason D. Christie
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality.
Win Statistics in Pulmonary Arterial Hypertension Clinical Trials
Authors: Jason Weatherald, Jude Moutchia, Nadine Al-Naamani, Robyn L. McClelland, Corey E. Ventetuolo, Harold I. Palevsky, Michael O. Harhay, Steven M. Kawut
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Win Statistics in Pulmonary Arterial Hypertension Clinical Trials." American Journal of Respiratory and Critical Care Medicine, 208(11), pp. 1231–1234
Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO)
Authors: Giulio Francolini, Andrea Gaetano Allegra, Beatrice Detti, Vanessa Di Cataldo, Saverio Caini, Alessio Bruni, Gianluca Ingrosso, Rolando Maria D'Angelillo, Anna Rita Alitto, Matteo Augugliaro, Luca Triggiani, Silvana Parisi, Gaetano Facchini, Marco Banini, Gabriele Simontacchi, Isacco Desideri, Icro Meattini, Richard K. Valicenti, Lorenzo Livi, Giulia Marvaso, Filippo Alongi, Fabio Arcidiacono, Andrea Lancia, Domenico Genovesi, Ciro Franzese, Giorgia Timon, Daniela Greto, Mauro Loi, Marianna Valzano, Pierluigi Bonomo, Monica Mangoni, Carlotta Becherini, Angiolo Tagliagambe, Raffaela Doro, Laura Masi
Journal: Journal of Clinical Oncology (2023)

PURPOSE ARTO (ClinicalTrials.gov identifier: NCT03449719 ) is a multicenter, phase II randomized clinical trial testing the benefit of adding stereotactic body radiation therapy (SBRT) to abiraterone acetate and prednisone (AAP) in patients with oligometastatic castrate-resistant prostate cancer (CRPC). MATERIALS AND METHODS All patients were affected by oligometastatic CRPC as defined as three or less nonvisceral metastatic lesions. Patients were randomly assigned 1:1 to receive either AAP alone (control arm) or AAP with concomitant SBRT to all the sites of disease (experimental arm). Primary end point was the rate of biochemical response (BR), defined as a prostate-specific antigen (PSA) decrease ≥50% from baseline measured at 6 months from treatment start. Complete BR (CBR), defined as PSA &lt; 0.2 ng/mL at 6 months from treatment, and progression-free survival (PFS) were secondary end points. RESULTS One hundred and fifty-seven patients were enrolled between January 2019 and September 2022. BR was detected in 79.6% of patients (92% v 68.3% in the experimental v control arm, respectively), with an odds ratio (OR) of 5.34 (95% CI, 2.05 to 13.88; P = .001) in favor of the experimental arm. CBR was detected in 38.8% of patients (56% v 23.2% in the experimental v control arm, respectively), with an OR of 4.22 (95% CI, 2.12 to 8.38; P &lt; .001). SBRT yielded a significant PFS improvement, with a hazard ratio for progression of 0.35 (95% CI, 0.21 to 0.57; P &lt; .001) in the experimental versus control arm. CONCLUSION The trial reached its primary end point of biochemical control and PFS, suggesting a clinical advantage for SBRT in addition to first-line AAP treatment in patients with metastatic castration-resistant prostate cancer.
Regulatory Challenges: Is a Surrogate End Point Instead of Overall Survival Enough for Regulatory Approval of (Neo)Adjuvant Cancer Treatment? The Swissmedic Perspective
Authors: Matea Pavic, Anita Wolfer, Qiyu Li, Arunas Gircys, Stephanie Juritz, Andreas Wicki, Thomas Cerny, Ulrich-Peter Rohr
Journal: Journal of Clinical Oncology (2023)

Surrogate end point only is not enough—the Swiss regulator`s perspective on (neo)adjuvant trials.
Suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: individual participant data meta-analysis
Authors: Nandita Perumal, Dongqing Wang, Anne Marie Darling, Enju Liu, Molin Wang, Tahmeed Ahmed, Parul Christian, Kathryn G Dewey, Gilberto Kac, Stephen H Kennedy, Vishak Subramoney, Brittany Briggs, Wafaie W Fawzi
Journal: BMJ (2023)

Abstract Objective To estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries. Design Individual participant data meta-analysis. Setting Prospective pregnancy studies from 24 low and middle income countries. Main outcome measures Nine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death. Analysis methods A systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes. Results Overall, 55% of participants had severely inadequate (&lt;70%) or moderately inadequate (70% to &lt;90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ 2 =0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ 2 =0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ 2 =0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ 2 =0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ 2 =0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ 2 =0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ 2 =0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy. Conclusions Inadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.
Histone deacetylase inhibitors modulate hormesis in leukemic cells with mutant FMS-like tyrosine kinase-3
Authors: Yanira Zeyn, Kristin Hausmann, Melisa Halilovic, Mandy Beyer, Hany S. Ibrahim, Walburgis Brenner, Siavosh Mahboobi, Matthias Bros, Wolfgang Sippl, Oliver H. Krämer
Journal: Leukemia (2023)

The FMS-like tyrosine kinase-3 (FLT3) is mutated in ~30% of acute myeloid leukemia (AML) patients.Common FLT3 mutations are internal tandem duplications (FLT3-ITD) and point mutations in its c-terminal tyrosine kinase domain (FLT3-TKD).The resulting active FLT3 receptors promote cell proliferation and resistance to programmed cell death (apoptosis) [1].The poor prognosis of patients with FLT3-ITD has spurred an intensive search for FLT3 inhibitors (FLT3i) [2].These include the nanomolar FLT3i quizartinib, which has produced promising benefits in AML patients with FLT3-ITD [3].TKD mutations in FLT3-ITD arise during the therapy of patients with quizartinib and confer drug resistance.The broad-range tyrosine kinase inhibitors midostaurin and gilteritinib are used with standard chemotherapy to treat AML.Their pleiotropic actions frequently evoke hematological toxicity [1, 2].Marbotinib is a hybrid FLT3i containing elements of quizartinib and bis(1H-indol-2-yl)methanone.Marbotinib specifically inhibits FLT3-ITD and FLT3-TKD [4, 5].Epigenetic modifiers of the histone deacetylase (HDAC) family control the development and survival of blood cells.Compared to normal cells, certain leukemic cell types frequently have aberrant expression levels and activities of epigenetic modifiers that belong to the histone deacetylase (HDAC) family.Accordingly, inhibitors of zinc-dependent HDACs (HDACi) are approved drugs for the treatment of subtypes of leukemia and lymphoma.These agents are vorinostat, romidepsin, belinostat, and chidamide.Further HDACi are tested clinically (www.clinicaltrials.org),such as the benzamide entinostat (MS-275) [6, 7].HDACi decrease FLT3-ITD through ubiquitin-dependent proteasomal degradation and apoptosis-associated caspase activation.Combinations of HDACi and FLT3i synergistically kill FLT3-ITD-positive cells through accelerated elimination of FLT3-ITD and DNA replication stress/ DNA damage induction.HDAC1, HDAC2, and particularly HDAC3 maintain the stability of FLT3-ITD [8].A cellular self-digestion process termed autophagy also eliminates FLT3-ITD [9].Nonetheless, autophagy can promote FLT3i resistance [10, 11].HDACs
BMA calls for investigation into debacle over covid and flu vaccinations
Authors: Zosia Kmietowicz
Journal: BMJ (2023)

BMA calls for investigation into debacle over covid and flu vaccinations Zosia KmietowiczThe BMA's GP committee has called for NHS England to investigate the mismanagement of this year's winter covid-19 and flu vaccination programmes, which it says has caused widespread confusion among GPs and risked patient safety.
PD-1 Blockade Induces Reactivation of Nonproductive T-Cell Responses Characterized by NF-κB Signaling in Patients with Pancreatic Cancer
Authors: Lestat R. Ali, Patrick J. Lenehan, Victoire Cardot-Ruffino, Andressa Dias Costa, Matthew H.G. Katz, Todd W. Bauer, Jonathan A. Nowak, Brian M. Wolpin, Thomas A. Abrams, Anuj Patel, Thomas E. Clancy, Jiping Wang, Joseph D. Mancias, Matthew J. Reilley, Chee-Chee H. Stucky, Tanios S. Bekaii-Saab, Rawad Elias, Nipun Merchant, Craig L. Slingluff, Osama E. Rahma, Stephanie K. Dougan
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease in which bulky tumor burden and limited time to develop antitumor T cells may have contributed to poor clinical efficacy. Here, we evaluated peripheral blood and tumor T cells from patients with PDAC receiving neoadjuvant chemoradiation plus anti–PD-1 (pembrolizumab) versus chemoradiation alone. We analyzed whether PD-1 blockade successfully reactivated T cells in the blood and/or tumor to determine whether lack of clinical benefit could be explained by lack of reactivated T cells versus other factors. Experimental Design: We used single-cell transcriptional profiling and TCR clonotype tracking to identify TCR clonotypes from blood that match clonotypes in the tumor. Results: PD-1 blockade increases the flux of TCR clonotypes entering cell cycle and induces an IFNγ signature like that seen in patients with other GI malignancies who respond to PD-1 blockade. However, these reactivated T cells have a robust signature of NF-κB signaling not seen in cases of PD-1 antibody response. Among paired samples between blood and tumor, several of the newly cycling clonotypes matched activated T-cell clonotypes observed in the tumor. Conclusions: Cytotoxic T cells in the blood of patients with PDAC remain sensitive to reinvigoration by PD-1 blockade, and some have tumor-recognizing potential. Although these T cells proliferate and have a signature of IFN exposure, they also upregulate NF-κB signaling, which potentially counteracts the beneficial effects of anti–PD-1 reinvigoration and marks these T cells as non-productive contributors to antitumor immunity. See related commentary by Lander and DeNardo, p. 474
Near-Infrared Spectral Tomography for Predicting Residual Cancer Burden during Early-Stage Neoadjuvant Chemotherapy for Breast Cancer
Authors: Xu Cao, Kristen E. Muller, Mary D. Chamberlin, Jiang Gui, Peter A. Kaufman, Gary N. Schwartz, Roberta M. diFlorio-Alexander, Brian W. Pogue, Keith D. Paulsen, Shudong Jiang
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The aim of this study is to investigate whether near-infrared spectral tomography (NIRST) might serve as a reliable prognostic tool to predict residual cancer burden (RCB) in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC) based upon early treatment response measurements. Experimental Design: A total of thirty-five patients with breast cancer receiving NAC were included in this study. NIRST imaging was performed at multiple time points, including: before treatment, at end of the first cycle, at the mid-point, and post-NAC treatments. From reconstructed NIRST images, average values of total hemoglobin (HbT) were obtained for both the tumor region and contralateral breast at each time point. RCB scores/classes were assessed by a pathologist using histologic slides of the surgical specimen obtained after completing NAC. Logistic regression of the normalized early percentage change of HbT in the tumor region (ΔHbT%) was used to predict RCB and determine its significance as an indicator for differentiating cases within each RCB class. Results: The ΔHbT% at the end of the first cycle, as compared with pretreatment levels, showed excellent prognostic capability in differentiating RCB-0 from RCB-I/II/III or RCB-II from RCB-0/I/III (P &amp;lt; 0.001). Corresponding area under the curve (AUC) values for these comparisons were 0.97 and 0.94, and accuracy values were 0.90 and 0.83, respectively. Conclusions: NIRST holds promise as a potential clinical tool that can be seamlessly integrated into existing clinical workflow within the infusion suite. By providing early assessment of RCB, NIRST has potential to improve breast cancer patient management strategies.
PERK Inhibition by HC-5404 Sensitizes Renal Cell Carcinoma Tumor Models to Antiangiogenic Tyrosine Kinase Inhibitors
Authors: Michael E. Stokes, Veronica Calvo, Sho Fujisawa, Crissy Dudgeon, Sharon Huang, Nupur Ballal, Leyi Shen, Jennifer Gasparek, Matthew Betzenhauser, Simon J. Taylor, Kirk A. Staschke, Alan C. Rigby, Mark J. Mulvihill, Nandita Bose, Eric S. Lightcap, David Surguladze
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Tumors activate protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK, also called EIF2AK3) in response to hypoxia and nutrient deprivation as a stress-mitigation strategy. Here, we tested the hypothesis that inhibiting PERK with HC-5404 enhances the antitumor efficacy of standard-of-care VEGF receptor tyrosine kinase inhibitors (VEGFR-TKI). Experimental Design: HC-5404 was characterized as a potent and selective PERK inhibitor, with favorable in vivo properties. Multiple renal cell carcinoma (RCC) tumor models were then cotreated with both HC-5404 and VEGFR-TKI in vivo, measuring tumor volume across time and evaluating tumor response by protein analysis and IHC. Results: VEGFR-TKI including axitinib, cabozantinib, lenvatinib, and sunitinib induce PERK activation in 786-O RCC xenografts. Cotreatment with HC-5404 inhibited PERK in tumors and significantly increased antitumor effects of VEGFR-TKI across multiple RCC models, resulting in tumor stasis or regression. Analysis of tumor sections revealed that HC-5404 enhanced the antiangiogenic effects of axitinib and lenvatinib by inhibiting both new vasculature and mature tumor blood vessels. Xenografts that progress on axitinib monotherapy remain sensitive to the combination treatment, resulting in ∼20% tumor regression in the combination group. When tested across a panel of 18 RCC patient-derived xenograft (PDX) models, the combination induced greater antitumor effects relative to monotherapies. In this single animal study, nine out of 18 models responded with ≥50% tumor regression from baseline in the combination group. Conclusions: By disrupting an adaptive stress response evoked by VEGFR-TKI, HC-5404 presents a clinical opportunity to improve the antitumor effects of well-established standard-of-care therapies in RCC.
Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22–00
Authors: Andrea Joaquin Garcia, Mattia Rediti, David Venet, Samira Majjaj, Roswitha Kammler, Elisabetta Munzone, Lorenzo Gianni, Beat Thürlimann, István Laáng, Marco Colleoni, Sherene Loi, Giuseppe Viale, Meredith M. Regan, Laurence Buisseret, Françoise Rothé, Christos Sotiriou
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To explore whether specific triple-negative breast cancer (TNBC) molecular subtypes are predictive for a benefit from maintenance low-dose cyclophosphamide and methotrexate (CM) in the adjuvant IBCSG 22–00 phase III clinical trial. Experimental Design: RNA sequencing was performed on a selection of 347 TNBC formalin-fixed paraffin-embedded (FFPE) tumor samples following a case–cohort-like sampling. TNBC subtypes were computed on gene expression data. The association between TNBC subtypes and treatment outcome was assessed using a Cox proportional-hazards interaction test. Results: Immunomodulatory (IM) and basal-like/immune activated (BLIA) molecular subtypes showed a significant survival benefit when treated with low-dose CM [disease-free survival (DFS): HR, 0.5; 95% confidence interval (CI), 0.28–0.89; Pinteraction = 0.018 and HR, 0.49; 95% CI, 0.27–0.9; Pinteraction = 0.021]. Moreover, a high expression of regulatory T-cell immune signature was associated with a better prognosis in the CM arm, in line with a potential immunomodulating role of cyclophosphamide. In contrast, a worse outcome was observed in tumors with a mesenchymal (M) subtype treated with low-dose CM (DFS: HR, 1.9; 95% CI, 1.2–3; Pinteraction = 0.0044). Conclusions: Our results show a differential benefit of low-dose CM therapy across different TNBC subtypes. Low-dose CM therapy could be considered as a potential strategy for TNBC tumors with IM subtype in the early-disease setting.